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Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue
Published on: November 30, 2018
Histone H3 specific acetyltransferases are essential for cell cycle progression
1Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Genes & Development
|December 4, 2001
Summary
Histone acetylation is crucial for cell function. Simultaneous loss of two H3-specific histone acetyltransferases (HATs), Sas3p and Gcn5p, is lethal, revealing essential overlapping roles in regulating H3 acetylation and cell cycle progression.
Area of Science:
- Molecular Biology
- Epigenetics
- Cell Biology
Background:
- Histone acetylation, particularly of H3 and H4, is vital for eukaryotic cell function.
- Loss of the H4-specific histone acetyltransferase (HAT) Esa1p in yeast causes cell cycle defects and lethality.
- Several yeast HATs target histone H3, but their catalytic subunits are not essential, creating a paradox regarding H3 acetylation's significance.
Purpose of the Study:
- To investigate the hypothesis that histone H3 acetylation is essential and mediated by the combined action of multiple HATs.
- To resolve the apparent discrepancy between the essentiality of H4 acetylation and the non-essentiality of individual H3 HATs.
Main Methods:
- Investigated the functional redundancy and essentiality of histone acetyltransferases (HATs) Sas3p and Gcn5p in Saccharomyces cerevisiae.
- Utilized genetic disruption (simultaneous knockout) of SAS3 and GCN5 genes to assess synthetic lethality and acetyltransferase activity.
- Analyzed global H3 acetylation patterns and cell cycle progression (G2/M arrest) following combined HAT gene disruption.
Main Results:
- Simultaneous disruption of SAS3 and GCN5, encoding H3-specific HATs, resulted in synthetic lethality, indicating essential overlapping functions.
- This synthetic lethality was specific to the combination of Sas3p and Gcn5p, not observed with other MYST family or H3-specific HATs.
- Combined loss of Gcn5p and Sas3p led to a global decrease in H3 acetylation and a cell cycle arrest in the G2/M phase.
Conclusions:
- The essentiality of H3 acetylation is maintained through the combined activities of specific HATs, notably Sas3p and Gcn5p.
- The overlapping functions of these H3 HATs are critical for viability, mirroring the essential role of the single H4 HAT, Esa1p.
- These findings underscore the fundamental biological importance of both H3 and H4 acetylation in chromatin regulation and cell cycle control.
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